Tuneable Permeability of Cellulose Nanofibrils‐based Membranes in Next‐Generation Barrier‐On‐Chip Systems

Barriers in the human body play a crucial role in regulating the exchange of substances between compartments, with permeability alterations occurring under both physiological and pathological conditions. In vitro barrier models are essential tools for studying the mechanisms of molecular diffusion across these barriers. Traditional coculture systems or advanced organ‐on‐chip (OoC) platforms mostly utilize permeable membranes based on artificial, nonbiodegradable materials. In this study, we introduced cellulose nanofibrils (CNFs)‐based membranes to develop a new class of in vitro barrier systems. CNFs, derived from natural sources, are nontoxic, biodegradable, optically transparent, and feature a 3D fibrillar structure that mimics the cellular basement membrane. We successfully modulated the permeability of CNF‐based membranes, interposed in dual‐chamber polydimethylsiloxane devices, to small molecules through chemical and enzymatic treatments, while preserving their ability to allow cell adhesion and growth. This technology holds potential for its integration in next‐generation OoC devices, offering more realistic and complex models that closely mimic the physiological behavior of human barriers.